Biology subjects

Frank, K.

Publications and source records attributed to Frank, K..

7 recordsLinked to original sources

bioRxiv2026

CXCR6⁺ natural killer cell immunotherapy preserves CD4⁺ T helper cells in humanized mice

Human immunodeficiency virus (HIV) persists despite antiretroviral therapy because long-lived viral reservoirs are not eliminated, and ongoing or rebound infection contributes to progressive loss of CD4 T helper cells. Natural killer (NK) cells can acquire adaptive, antigen-experienced functions, including recall responses to HIV envelope protein, suggesting that defined NK-cell subsets may be therapeutically useful against HIV. Because HIV-responsive adaptive NK-cell activity is enriched among CXC chemokine receptor 6-positive (CXCR6) NK cells, we tested whether CXCR6 NK cells provide enhanced antiviral activity and CD4 T-cell protection compared with CXCR6- NK cells. In co-cultures with HIV-infected primary CD4 T cells, PBMC-derived CXCR6 and CXCR6- NK cells both reduced viral replication, but CXCR6 NK cells mediated significantly greater suppression. In HIV-infected humanized mice, weekly infusion of expanded PBMC-derived NK cells lowered plasma viral burden, with CXCR6 NK cells providing stronger preservation of circulating CD4 T cells and significant preservation of splenic CD4 T cells. HIV-Env vaccination further enriched NK cells with enhanced therapeutic activity. CXCR6 NK cells derived from HIV-Env-vaccinated humanized mice produced the strongest suppression of HIV replication and restored CD4 T-cell frequencies in blood and spleen to levels comparable to uninfected controls. Together, these findings identify CXCR6 NK cells as an HIV-responsive adaptive NK-cell subset that combines antiviral activity with preservation of CD4 T-cell immunity in vivo. These data support further development of CXCR6 NK-cell therapy as a vaccine-informed cellular immunotherapy strategy for HIV.

immunology↗

bioRxiv2025

CDM1 is required for meiotic progression and genome integrity during male meiosis in Arabidopsis

Microsporogenesis involves the integration of meiosis with the developmental program leading to formation of microspores from meiocytes. The CALLOSE DEFICIENT MICROSPORE 1 (CDM1) gene of Arabidopsis has been previously characterized as being required for callose metabolism and its loss results in defects in microspore wall development, degeneration of meiotic products, and male sterility. We report here that CDM1 is required for normal meiosis I progression, meiotic chromosome organization, and maintenance of DNA integrity. CDM1 is part of the ATM dependent DNA damage response in dividing vegetative tissues. The cdm1 mutant shows defects in meiotic chromosome condensation, arrest at metaphase I, susceptibility to chromosome breakage in rDNA regions, defects in positioning of the products of meiosis, and increased expression of recombination related genes. However, fidelity of chromosome segregation is not affected. Furthermore, the meiotic phenotype of cdm1 is independent of SPO11 induced meiotic double strand breaks. CDM1 protein displays granular localization in meiosis throughout the cytoplasm that resembles that of mRNP granules. The results show that CDM1 is required for maintenance of proper chromosome organization and DNA integrity in the course of male meiosis. The chromosomal defects in cdm1 may originate from regions of defective or incomplete replication. HighlightCDM1 expression is DNA damage inducible in Arabidopsis mitotic cells. CDM1 is required for genome integrity in male meiosis independent of SPO11-induced DNA breaks, suggesting a role in regulation of premeiotic replication repair.

plant biology↗

bioRxiv2025

A Signaling Hub in the Mosquito Rectum Coordinates Reproductive Investment After Blood Feeding

After a blood meal, female Aedes aegypti mosquitoes suppress host-seeking while converting ingested nutrients into yolk protein for egg development. Neuropeptide Y-like Receptor 7 (NPYLR7) is required for this behavioral switch, but its physiological role and sites of action were unknown. We identify a specialized, non-neuronal population of npylr7-expressing cells in the rectal pads of the mosquito hindgut. While this tissue is associated with fluid and ion balance, npylr7 mutants maintain fluid regulation but show impaired oocyte provisioning. These cells display neuroendocrine features, including calcium responses to the NPYLR7 ligand RYamide and amino acids, as well as expression of neurotransmitter synthesis and vesicle release machinery. Vesicle recruitment occurs in these cells post-blood meal in wild-type, but not npylr7 mutants. Our findings reveal an unexpected role for NPYLR7 in a rectal cell population senses nutritional cues and communicates with the nervous system to regulate reproductive physiology, paralleling gut-brain circuits in mammals.

neuroscience↗

bioRxiv2025

c-Rel drives pancreatic cancer metastasis through Fibronectin-Integrin signaling-induced isolation stress resistance and EMT activation

Pancreatic ductal adenocarcinoma remains one of the deadliest malignancies, with limited treatment options and a high recurrence rate. Recurrence happens often with metastasis, for which cancer cells must adapt to isolation stress to successfully colonize distant organs. While the fibronectin-integrin axis has been implicated in this adaptation, its regulatory mechanisms require further elaboration. Here, we identify c-Rel as an oncogenic driver in PDAC, promoting epithelial-to-mesenchymal transition (EMT) plasticity, extracellular matrix (ECM) remodeling, and resistance to isolation stress. Mechanistically, c-Rel directly regulates fibronectin (Fn1) and CD61 (itgb3) transcription, enhancing cellular plasticity and survival under anchorage-independent conditions. Fibronectin is not essential for EMT, but its absence significantly impairs metastatic colonization, highlighting a tumor-autonomous role for FN1 in isolation stress adaptation. These findings establish c-Rel as a key regulator of PDAC metastasis by controlling circulating tumor cell (CTC) niche and survival, suggesting that targeting the c-Rel-fibronectin-integrin axis could provide new therapeutic strategies to mitigate disease progression and recurrence.

cancer biology↗

bioRxiv2025

TRAIL-mediated PMN-MDSC depletion prevents CD4+ T cell loss in HIV-infectedhumanized mice

Myeloid-derived suppressor cells (MDSCs) are critical regulators of HIV immunity, but the mechanisms behind their expansion and value as a therapeutic target remain unclear. We investigated MDSC function in HIV using a humanized mouse model. Acute HIV-1 infection triggered the systemic expansion of polymorphonuclear MDSCs (PMN-MDSCs), with their frequency correlating positively with plasma viral load. Notably, PMN-MDSC expansion increased further when natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) were depleted, suggesting these immune cells restrain MDSC proliferation. We identified Tumor necrosis factor related apoptosis-inducing ligand (TRAIL)-induced apoptosis as a regulatory mechanism, as MDSCs expressed high levels of TRAIL receptor 2 (R2), while NK cells and CTLs upregulated TRAIL expression during HIV infection. Treating HIV-1-infected mice with a TRAIL-R2 agonist significantly reduced MDSC levels to those of uninfected mice and significantly improved NK cell and CTL immune function. Crucially, in viremic humanized mice, the treatment prevented CD4+ T cell loss, a hallmark of HIV-1 pathogenesis and acquired immune deficiency syndrome (AIDS) progression. These findings reveal the therapeutic potential of targeting MDSC apoptosis to mitigate CD4+ T cell depletion and enhance HIV-specific immunity, offering a new clinical target to prevent AIDS and insights into MDSC- NK/CTL cross-regulation during HIV-1 infection.

immunology↗

bioRxiv2020

Alcohol dependence promotes systemic IFN-γ and IL-17 responses in mice

Alcohol use disorder (AUD) is a chronic relapsing disorder characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences. AUD is associated with a variety of physiological changes and is a substantial risk factor for numerous diseases. We aimed to characterize systemic alterations in immune responses using a mouse model of chronic intermittent alcohol exposure to induce alcohol dependence. We exposed mice to chronic intermittent ethanol vapor for 4 weeks and used multiparametric flow cytometry to analyze the expression of cytokines IFN-{gamma}, IL-4, IL-10, IL-12 and IL-17 by different immune cells in the blood, spleen and liver of alcohol dependent and non-dependent control mice. We found increases in IFN-{gamma} and IL-17 expression in a cell type- and organ-specific manner. Often, B cells and neutrophils are primary contributors to increased IFN-{gamma} and IL-17 levels while other cell types play a secondary role. We conclude that chronic alcohol exposure promotes systemic pro-inflammatory IFN-{gamma} and IL-17 responses in mice. These responses are likely important in the development of alcohol-related diseases, but further characterization is necessary to understand the initiation and effects of systemic inflammatory responses to chronic alcohol exposure.

immunology↗

bioRxiv2020

An Inexpensive RT-PCR Endpoint Diagnostic Assay for SARS-CoV-2 Using Nested PCR: Direct Assessment of Detection Efficiency of RT-qPCR Tests and Suitability for Surveillance

With a view to extending testing capabilities for the ongoing SARS-CoV-2 pandemic we have developed a test that lowers cost and does not require real time quantitative reverse transcription polymerase chain reaction (RT-qPCR). We developed a reverse transcription nested PCR endpoint assay (RT-nPCR) and showed that RT-nPCR has comparable performance to the standard RT-qPCR test. In the course of comparing the results of both tests, we found that the standard RT-qPCR test can have low detection efficiency (less than 50%) in a real testing scenario which may be only partly explained by low viral representation in many samples. This finding points to the importance of directly monitoring detection efficiency in test environments. We also suggest measures that would improve detection efficiency.

molecular biology↗